H5N1 avian flu virus 'could spread in people'

“Bird flu 'could mutate to cause deadly human pandemic',” BBC News has reported. The BBC says that Dutch researchers have identified mutations that could allow the H5N1 virus to spread rapidly in humans. The tone of the headlines is somewhat alarmist for coverage of a theoretical risk. Nevertheless, this is a controversial study, with the researchers having rebuffed requests from a US bioterrorism prevention agency to limit the publication of their findings.

H5N1, the “bird flu” virus, has caused several outbreaks among wild birds and domesticated poultry. H5N1 can, but usually doesn’t, affect humans and, so far, it has not been shown to spread between people. However, it is possible that genetic mutations could change the virus so that it could spread between humans.

The current research – in ferrets – looked at whether H5N1 in its normal form or in genetic variants could be spread between ferrets by airborne transmission (that is by sneezing or breathing). The researchers found that, while the wild type could not be passed by airborne transmission, some of the mutated viruses could spread, and these shared five key mutations. None of the ferrets died after airborne infection with the mutant H5N1 viruses. The researchers found that the mutated virus was sensitive to the flu drug Tamiflu, and ferrets that had been given an H5N1 vaccine produced antibodies against the mutant strains.

This lab research provides some evidence that it may be possible for the bird flu virus to acquire mutations that could allow it to spread between people via respiratory droplets. However, this research should not cause alarm as these mutations have not arisen naturally in the wild, they have only been created in the lab.

The findings will help national public health agencies that monitor influenza viruses, allowing them to make plans to cope with the next epidemic or pandemic flu that may emerge in humans.

Where did the story come from?

The study was carried out by researchers from Erasmus Medical Center, The Netherlands, the University of Cambridge, and US National Institutes of Health. Funding sources included the National Institutes of Health. The study was published in the peer-reviewed journal, Science.

While the BBC’s headline presented the most threatening issue to stem from the research, overall, the media gave a fair representation of this research. However, there has been considerable media coverage of the ongoing controversy over the publication of all of the research against the advice of the US National Science Advisory Board for Biosecurity.

What kind of research was this?

This laboratory research looked at whether genetic mutations in the H5N1 “bird flu” virus would allow it to spread between mammals via airborne transmission (that is by sneezing and breathing). Currently, H5N1 isn’t spread in this way between humans, but if it were it would be more contagious. All human epidemic and pandemic flu strains in the past century have been able to spread by airborne transmission.

H5N1 is one of many subtypes of the influenza A virus. It is the variant that has been identified in the majority of poultry outbreaks over the past decade. It is also the cause of most of the rare cases of infection in humans who have had contact with infected birds. However, to date there has been limited evidence of transmission of H5N1 between humans, and the virus can’t be transmitted by airborne droplets.

The research was carried out in ferrets because they are susceptible to both bird and human flu viruses. The researchers created a number of genetically altered variants of H5N1 to see whether these mutations could result in a virus that could be spread between the ferrets by airborne droplets.

Animal research such as this is useful for investigating how viruses can spread between mammals, because it gives us clues to how viruses can also spread between humans.

What did the research involve?

The research involved a series of experiments using an H5N1 strain that was isolated in Indonesia, and genetically modified variants of this strain. The variants had been engineered to have mutations that the researchers predicted might help them to spread through the air.

In the first experiment, the researchers took four groups of six ferrets. Into the noses of one group of ferrets they put the H5N1 virus, and into the other three they put three mutant variants of H5N1. On the third and seventh days they measured levels of the virus in the ferrets’ noses, throats, windpipes and lungs.

In the second experiment, the researchers had housed four uninfected ferrets in cages adjacent to those ferrets infected with an H5N1 variant, to see if the viruses would spread without direct contact. When the researchers found no airborne transmission of the viruses, they designed a third experiment to ‘force’ the virus to adapt to replicating in the ferrets’ respiratory system. To do this they carried out a process called “passaging” where viruses are passed from one ferret to the next a number of times. This encourages natural accumulation of mutations, and they hoped some would help the virus to be transmitted in an airborne fashion.

They started this experiment by giving one ferret the normal H5N1 virus, and one a genetic variant. They collected samples from the noses of these ferrets and gave another two ferrets their respective samples. This was repeated for a total sequence of 10 new ferrets for both the normal and genetic variant viruses. The nasal samples from the 10th set of ferrets were then tested in a further experiment to see whether these viruses could cause airborne transmission.

In this experiment the samples were used to infect six more ferrets. Non-infected ferrets were then placed in cages adjacent to, but separate from, each infected ferret. They then took samples from the non-infected ferrets to see whether they had become infected by airborne transmission.

Once they found H5N1 variants that could be transmitted in an airborne fashion, they looked at their genetic make-up to identify which mutations had allowed them to spread through the air. They also tested whether these viruses were susceptible to antiviral drugs, and whether ferrets that had been given an H5N1 vaccine could produce antibodies against the mutant strains.

What were the basic results?

The researchers found that the ‘normal’ H5N1 virus acquired mutations as it passed along the 10 ferrets. However, they found no evidence that this virus was able to spread via airborne transmission to the neighbouring ferrets. By contrast, they found that three out of four of the ferrets neighbouring those inoculated with the mutant H5N1 line did become infected with H5N1 as a result of airborne transmission. None of the ferrets died as a result of this airborne transmission.

All of the viruses that were able to spread through the air had the three mutations that the researchers had engineered, plus another two naturally acquired mutations affecting the same protein. The viruses had other mutations, but these were not shared by all the airborne-spread viruses.

They also found that when they tested one of the airborne viruses it was similarly sensitive to the antiviral drug Tamiflu (oseltamivir) as the normal H5N1 virus. They also showed that ferrets that had been given an H5N1 vaccine produced antibodies against the mutant strains.

How did the researchers interpret the results?

The researchers concluded that “avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals and therefore constitute a risk for human pandemic influenza”. They say that while they have proved that the virus can be transmitted though the air, they cannot say if it is an efficient mode of transmission. They also caution that further research is needed to help prepare for a pandemic.

Conclusion

This is valuable yet controversial scientific research. It has explored whether genetic variants of the H5N1 bird flu virus can acquire mutations allowing the virus to spread through the air between mammals such as humans.

H5N1 is the “bird flu” virus and has been the cause of several outbreaks among wild birds and domestic poultry. While it does not usually affect humans, rare cases have occurred in people in close contact with infected poultry. So far it has not been demonstrated to be capable of spreading through the air between people. To test whether genetic mutations could enable this to happen, researchers tested H5N1 variants on ferrets. They found that airborne transmission of the mutant variants was possible, although none of the ferrets died after being infected with the mutant H5N1 viruses this way. The researchers also noted that one of the mutated viruses was similarly sensitive to Tamiflu as the “normal” H5N1 virus. Ferrets given an H5N1 vaccine could produce antibodies against the mutant strains.

This lab research provides some evidence that it is theoretically possible for the bird flu virus to acquire mutations that could allow it to spread between mammals by coughs, sneezes and breathing. This may mean that a mutated form of bird flu could also spread between humans.

The news is not a cause for alarm, as these mutations have not yet arisen in the wild. This information may help national public health agencies which monitor influenza, enabling them to make plans about how to cope with the next epidemic or pandemic flu that may emerge in humans.